The Exercise, Nutrition, and Healthy Lifestyle Research Group at the INCLIVA Health Research Institute in Valencia has led a study that provides new evidence on the role of mitochondria—the cellular structures responsible for producing energy in our cells—in age-related muscle decline.

The results, published in the scientific journal Proceedings of the National Academy of Sciences (PNAS), demonstrate that mitochondrial dysfunction directly contributes to the loss of strength and functional capacity, as well as the development of frailty in older adults. Furthermore, the study shows that physical exercise can partially reverse this decline as a therapeutic strategy to preserve muscle health, maintain functional capacity, and promote healthier aging.

Frailty is one of the major challenges associated with aging. As life expectancy increases, so does the number of older adults experiencing loss of strength, fatigue, reduced mobility, and a greater risk of falls and hospitalizations. It is estimated that it affects approximately one in ten people over 65 and almost half of those over 85. This progressive loss of muscle mass and strength not only reduces autonomy and quality of life but also increases dependence and the burden on healthcare systems. Therefore, maintaining functional capacity has become a priority in both geriatric medicine and aging research.

The role of mitochondria and the effect of exercise

Although it is not fully understood why some people age while maintaining good physical capacity and quality of life, while others develop frailty, mitochondria are one of the key factors in this process. The study demonstrates that their deterioration is closely related to the loss of muscle function. Researchers analyzed their role during aging and observed that their decline contributes to the age-related loss of functional capacity. However, the results also indicate that this process is not irreversible. Physical exercise has proven to be a highly effective tool for preserving mitochondrial function and physical performance during aging, even when training programs are initiated later in life.

“Mitochondria have a remarkable capacity for adaptation, are essential for cellular function, and their deterioration contributes to age-related physical decline. In this context, physical exercise acts as a powerful stimulus for mitochondrial remodeling, improving muscle energy capacity and helping to preserve physical function during aging,” explains Dr. Mª Carmen Gómez Cabrera, principal investigator of the study, coordinator of the aforementioned INCLIVA group, researcher at the Biomedical Research Networking Center for Frailty and Healthy Aging (CIBERFES) of the Carlos III Health Institute (ISCIII), and Professor of Physiology at the University of Valencia (UV).

“The aim of this research was to determine whether mitochondrial dysfunction in skeletal muscle is directly linked to the functional decline associated with frailty and to assess whether muscle oxidative capacity inevitably decreases with age or whether it can be preserved through exercise. This question is important because frailty is one of the main factors of disability in older adults,” he adds.

A combined experimental and clinical approach

This research combined experimental animal models with analyses in people of different ages and fitness levels. In the preclinical phase, old mice were used, subjected to a multicomponent physical training program, as well as genetic models with reduced or enhanced mitochondrial function. Their physical performance, the presence of frailty, and multiple parameters related to mitochondrial function in muscle were evaluated.

In parallel, muscle biopsies from 30 people between 17 and 99 years of age were analyzed, studying indicators of muscle mass, mitochondrial activity, and oxidative stress. This approach allowed for the evaluation of both the biological mechanisms involved and their relevance to human aging.

Scientific collaboration and infrastructure

Researchers from the INCLIVA Research Group on Exercise, Nutrition and Healthy Lifestyle, the Biomedical Research Networking Center for Frailty and Healthy Aging (CIBERFES), the Biomedical Research Networking Center for Cardiovascular Diseases (CIBERCV), and the National Center for Cardiovascular Research (CNIC) of the Carlos III Health Institute, among other centers, participated in this work.

PNAS